What every physician needs to know about diabetes

Diabetes is a highly prevalent, chronic medical disorder that is present in approximately 25 - 30% of hospitalized patients, and approximately 20 - 25% of those admitted for elective and non-elective surgical procedures. While outpatient attention to glycemic control has been demonstrated to be associated with reduction in risk for diabetes related microvascular and neuropathic complications, short term attention to glycemic control during hospitalization is associated with reductions in morbidity, mortality, hospital length of stay (LOS), and need for readmission.

Patients with diabetes have a higher lifetime risk of undergoing a surgical procedure than those without diabetes. Appropriate glycemic management during the peri-operative time period helps to ensure optimal surgical and patient outcomes. Because diabetes is frequently associated with other metabolic disorders that increase the risk for cardiovascular disease, such as obesity, hypertension, and hyperlipidemia (see Chapter on Diabetes and Cardiovascular Disease), careful pre-operative assessment of potential cardiovascular risk factors in addition to glycemic control is indicated.

What else could the patient have?

Hyperglycemia, defined as any blood glucose level >140mg/dl, in the absence of a prior history of known diabetes, is associated with adverse outcomes in a variety of inpatient clinical settings. Potential causes of hyperglycemia in hospitalized patients include:

Unrecognized or newly diagnosed diabetes: In the United States, approximately 7 million individuals have diabetes and are unaware of it. There are even more patients with pre-diabetes who are at risk of developing hyperglycemia during periods of hospitalization or stress related to a surgical procedure. A diagnosis of diabetes can be made in patients with hyperglycemia who have an A1C ≥6.5. Classic symptoms of hyperglycemia may not always be reported in this group of patients.

Stress hyperglycemia refers to elevations in BG that occur during hospitalization and reverts to normal following hospital discharge. These patients will have an A1C of <6.5% and may be at risk for diabetes in the future.

Patients with and without diabetes may experience hyperglycemia as a result from stress, use of parenteral/enteral nutrition, use of concentrated dextrose infusions (i.e. ≥10% dextrose), or administration of hyperglycemia-provoking agents, such as glucocorticoids, vasopressors, or immunosuppressants.

Key laboratory and imaging tests

In patients with a history of diabetes, a history and physical exam will help determine appropriate management:

Does the patient have type 1, type 2, or another type of diabetes (See chapter on Diabetes Classification)

What is the patient’s outpatient diabetes regimen? (oral anti-diabetes agents (OAD), non-insulin injectable agents, insulin, or a combination of these).

If possible, determine outpatient doses and timing of administration with respect to meals.

Assess outpatient glycemic control.

What is the most recent A1C?

Order an A1C on any patient with diabetes who does not have this available at time of admission and on all patients with newly recognized hyperglycemia (BG > 140 mg/dl)

Does the patient perform self monitoring of blood glucose (SMBG)?

Is the patient experiencing frequent hyper or hypoglycemia?

Does the patient have pertinent medical co-morbidities that may impact glycemic control?

Does the patient have evidence of diabetes related complications, such as:

CKD, which increases the risk for cardiovascular disease/events.

Microalbuminuria or proteinuria, which can be markers of underlying CVD.

Autonomic neuropathy, which increases the risk for complications at the time of induction of anesthesia.

Assess patient knowledge about their diabetes self management regimen at home, including diet, exercise, awareness of hypoglycemia and hyperglycemia and how to treat.

Key laboratory and diagnostic tests

It is recommended that all patients have a BG determination at the time of either elective or non-elective hospitalization, independent of a prior known history of diabetes. Those without a prior history of diabetes who have BG <140 mg/dl may not require additional testing. All patients with a history of diabetes (if not documented in the last 2-3 months) and those who have BG ≥ 140 mg/dl without a prior known history of diabetes require determination of an A1C.

Some considerations regarding interpretation of A1C in hospitalized patients:

Results can be unreliable in patients with a shortened red blood cell lifespan, such as hemolysis, acute blood loss, or recent blood transfusions.

Higher than expected levels can be seen in patients with a longer red blood cell lifespan, such as those with iron deficiency.

Some considerations regarding capillary blood glucose monitoring:

All patients with a history of diabetes, newly diagnosed hyperglycemia, or risk factors for hyperglycemia require capillary BG (CBG) monitoring.

Some important considerations regarding the interpretation of data from bedside BG meters:

Currently available CBG monitoring devices produce results that can vary by approximately 20%, even when used appropriately.

Anemia (HCT < 25% for many meters although this varies) can cause spurious elevations in CBG.

A1C 7 - 8% is acceptable for surgical procedures. While evidence suggests that a preoperative A1C <7% is associated with the lowest risk for postoperative wound infections, there are many individuals (those of an older age, with underlying CVD, at high risk for hypoglycemia) who are not candidates for intensification of their glycemic control to an A1C <7%.

A1C > 8% is consistent with uncontrolled diabetes and reflects an average BG >180 mg/dl, a level at which prospective and retrospective data demonstrates higher incidence of infectious complications. Consideration should be given to improving glycemic control before proceeding with surgery as a way of minimizing risk for postoperative complications and mortality.

For non-elective or urgent surgical procedures:

It is not always possible to delay surgery in patients with A1C >8%. Examples of this would be an urgent need for a revascularization procedure in a patient with an acute coronary syndrome for whom urgent revascularization is indicated, or in cases of trauma. In these instances, determination of the pre-operative BG is indicated with initiation of an intravenous insulin infusion protocol titrated to maintain blood glucose values in a range of 140 - 180 mg/dl, as a way of minimizing risk for postoperative complications.

Other tests that may prove helpful diagnostically

EKG: Patients with diabetes have a high prevalence of underlying cardiovascular disease (CVD).

Many individuals with type 2 diabetes are obese, which is also an independent risk factor for CVD.

Routine non-invasive stress testing is not useful in identifying high risk subjects prior to surgery. However, patients with new EKG abnormalities are candidates for additional cardio-pulmonary evaluation.

Management and treatment of the Disease

As with any chronic disease management, the success of therapy is based on establishing therapeutic goals that help guide therapy. Fortunately, for patients with diabetes or newly recognized hyperglycemia, the goals are straightforward in that they target specific ranges of BG. The American Association of Clinical Endocrinologists together with the American Diabetes Association recently published a position statement recommending reasonable and safe glycemic targets that minimize risk for hypoglycemia and reduce the risks associated with sustained higher levels of BG.

For critically ill patients, a target range of 140 - 180mg/dl is recommended. A lower target range of 110 - 140mg/dl may be appropriate for SICU patients. For non-critically ill patients, the recommended fasting and preprandial BG target range is 100 - 140mg/dl, while the random glucose target is < 180mg/dl. More stringent targets may be appropriate for stable patients with previous tight glycemic control, and less stringent targets may be appropriate for those with severe co-morbidities or terminal illnes.

(See chapter on Outpatient Insulin Therapy for a list of currently available insulin products and their pharmacokinetic profiles.)

General principles of diabetes management

Bedside glucose monitoring is recommended for all patients with diabetes or newly recognized hyperglycemia.

Monitor BG levels before meals and bedtime in patients who are eating.

Monitor BG levels every 4 to 6 hours in patients who NPO or who are receiving continuous enteral or parenteral nutrition.

Adjust timing of BG monitoring according to administered nutritional therapy.

Oral and injectable non-insulin agents are usually not appropriate for treatment of hyperglycemia in the inpatient setting.

Insulin therapy:

Patients who are treated with insulin at home will require insulin therapy in the hospital.

Modify the pre-admission diabetes treatment regimen to avoid risk for hyperglycemia and hypoglycemia.

Sliding scale insulin (SSI) is NEVER appropriate as monotherapy in type 1 diabetes.

SSI as monotherapy is ineffective at achieving glycemic goals in the hospital.

Scheduled subcutaneous insulin therapy is recommended for treatment of hyperglycemia.

Patients in Critical Care Areas

IV insulin therapy is the optimal method for achieving glycemic control in the critical care setting. Continuous IV insulin infusions allow for timely titration of insulin in patients with changing clinical status and insulin sensitivity. The administration of IV insulin requires careful and frequent monitoring of glucose levels to achieve and maintain desired glycemic targets while also avoiding hypoglycemia.

Several IV insulin infusion protocols have been published. In general, the safest and most effective IV insulin protocols are those that take into account the current and previous BG and rate of insulin infusion to guide changes in insulin infusion rates. It is important to ensure that the selected or developed protocol is easy to order and follow, achieves glycemic goals in a reasonable time period, maintains these goals with minimal risk for hypoglycemia, and includes instructions for timely adjustments with changes in nutritional intake or clinical status.

Patients treated with IV insulin will require transition to scheduled SC insulin therapy as their clinical condition improves and they start eating regular meals. The initial dose and distribution of SC insulin at the time of transition is determined by the IV insulin requirement prior to transition, with consideration of the anticipated nutritional and clinical status and use of other medications.

It is important that SQ insulin is administered prior to discontinuation of IV insulin. IV insulin can be discontinued immediately after rapid acting insulin (RAI) is given, two hours after administration of regular insulin, and up to four hours following administration of intermediate or long acting insulin.

Patients in Non-Critical Care Areas

Scheduled subcutaneous insulin therapy is preferred for the majority of non-critically ill patients with hyperglycemia, even in patients not on insulin at home. The components of inpatient scheduled insulin therapy are similar to those described as basal bolus insulin therapy (BBI) for outpatients (see chapter on Outpatient Insulin Therapy) with some important considerations discussed below.

For patients previously treated with insulin at home prior to admission* (Insulin pump therapy discussed separately):

Patients with type 1 diabetes are usually taking BBI prior to admission.

Patients with type 2 diabetes may be one of several different insulin regimens prior to admission:

Once daily NPH, detemir, or glargine insulin in combination with OAD or non-insulin injectable therapy.

A basal bolus insulin.

Some patients with type 2 diabetes may be taking doses of basal insulin that exceed 1 unit per kg per day. Modification of this regimen is often required at the time of hospitalization.

*Not all patients will be able to provide information regarding the specific insulin or doses being used prior to admission. In these situations, it is reasonable to initiate or adjust insulin therapy.

The components of scheduled insulin therapy include:

Basal insulin: glargine, detemir, or NPH.

Nutritional insulin: regular, lispro, aspart, glulisine.

Correctional insulin: This is often referred to as supplemental or SSI.

Situations where correction insulin may be used as monotherapy for a short duration include:

Patients with no prior diabetes history and an elevated admission glucose.

Patients who begin therapy with glucocorticoids or enteral/parenteral nutrition.

Once a persistent insulin requirement is established, a change to scheduled subcutaneous insulin therapy is recommended.

All patients with diabetes are at risk for hyperglycemia during periods of hospitalization. As discussed above, OAD and injectable non-insulin agents are not appropriate for inpatient use in the majority of patients. For selected stable patients under good control who are ingesting regular meals and who do not have contraindications to their use, continued use may be acceptable.

For patients with diabetes treated with ODA or non-insulin injectable therapy or newly recognized hyperglycemia:

Initiate CBG monitoring with administration of insulin according to a low dose correctional insulin scale.

In patients in whom CBG monitoring shows most BG <140 mg/dl for 24 - 48 hours, no further therapy is needed and monitoring can be discontinued.

In patients with a persistent insulin requirement or with >2BG >180 in 24 hours, initiate scheduled insulin therapy.

Scheduled inpatient insulin therapy

It is difficult to know with certainty what the optimal insulin dosing schedule will be for an individual patient. There are now several publications demonstrating the safety and efficacy of a weight based insulin dosing strategy for inpatients with type 2 diabetes. These regimens calculate a total daily dose (TDD) of insulin of 0.4 - 0.5 units per kg per day, when taking both basal and bolus requirements into consideration. Patients with type 1 diabetes or those with renal insufficiency are often more insulin sensitive than those with type 2 diabetes, who are often obese, suggesting the need to start with lower weight based calculations of 0.2 - 0.3 units per kg.

The information provided below is meant to be used as a guideline for inpatient insulin management. Clinical judgment is an essential component of tailoring any insulin regimen to one that is both safe and effective for a specific patient.

Calculate the Total Daily Dose (TDD) of basal and nutritional insulin based on body weight.

0.3 units/kg/day for lean patients with type 1 diabetes or those with renal insufficiency.

0.5 units/kg/day for patients with type 2 diabetes who are overweight or obese

Administer 50% of TDD as basal and 50% as nutritional insulin

Patients who are NPO may require only the basal insulin component

Divide the nutritional component into three premeal insulin doses for patients who are eating.

Some hospitals have nursing personnel who are knowledgeable at carbohydrate counting and can assist patients in calculating premeal insulin doses. (See chapter on Outpatient Insulin Therapy.)

Order correctional insulin according to TDD.

Low dose: if TDD <40 units/day (typically used for lean patients or patients with T1DM)

Patient specific scales can be ordered for those with very low or high insulin requirements.

Specific clinical situations

Many of the regimens described below suggest use of regular over RAI insulin preparations. The reasons for this are based on the longer duration of action with regular insulin, which allow for less frequent dosing in patients who are not eating regular meals.

Enteral Nutrition Therapy

Patients who are receiving enteral nutrition will require insulin timed according to the administration of these formulas:

Continuous EN

Administer regular insulin every 6 hours alone or in combination with basal insulin administered every 12 to 24 hours.

Cycled EN

Option 1

Administer basal insulin at initiation of the EN.

Administer regular insulin at initiation and every 6 hours for duration of the cycled EN.

Correction: regular insulin q6h.

Option 2

NPH plus regular or 70/30 insulin at initiation of EN.

Administer regular insulin at initiation and every 6 hours for duration of the cycled EN.

Correction: regular insulin q6h.

Bolus EN

Give a fixed dose of nutritional insulin plus correction at time of bolus

Parenteral Nutrition Therapy

Patients who are receiving parenteral nutrition (PN) will require insulin timed according to the administration of these formulas:

Continuous PN

Include regular insulin in the administered PN formula at an initial dose of 1 unit for each 10 grams of carbohydrate, adjusted daily according to BG results and number of units of correction insulin.

Administer correction insulin every 4-6 hours alone or in combination with basal insulin administered every 12 to 24 hours.

Cycled PN

Include regular insulin in the administered PN formula at an initial dose of 1 unit for each 10 grams of carbohydrate, adjusted daily according to BG results and number of units of correction insulin.

Administer correction insulin every 4-6 hours alone or in combination with basal insulin administered at initiation of the PN formula.

Glucocorticoid Therapy

Hyperglycemia is common in patients who receive high dose glucocorticoids. While the optimal management of these patients has not been clearly defined, insulin is generally preferred. Insulin requirements vary among patients in response to steroid therapy and can be difficult to predict. Gradual persistent adjustments in insulin according to CBG results are recommended.

A suggested approach to insulin therapy in patients treated with high dose glucocorticoids is:

An alternative approach to the management of steroid associated hyperglycemia is to use a weight based dose of an intermediate or long acting insulin at the time steroid therapy is initiated, according to the algorithm suggested in Table I.

Table I.

Algorithm for a weight based dose of an intermediate or long acting insulin at the time steroid therapy is initiated

Prednisone Dose Equivalent (mg)

NPH Dose (units/kg)

10

0.1

20

0.2

30

0.3

>40

0.4

For persistent significant hyperglycemia (>350 mg/dl), more aggressive insulin therapy is indicated. Consider transferring the patient to a monitored setting for an IV insulin infusion, temporary use of a higher dose or more frequent (q4h) correction scale with rapid acting insulin, and/or obtaining a diabetes consult.

Insulin pump therapy

Patients who use an insulin pump as outpatients can sometimes continue this in the hospital provided that they have the mental and physical capacity to do so. The availability of hospital personnel who have familiarity with insulin pump therapy is important.

Patients who are unable to continue their insulin pump due to mental or physical impairments can be converted to scheduled subcutaneous insulin. The long-or intermediate-acting insulin dose approximates the total of all basal rates over a 24 hour period. The prandial insulin dose approximates the doses administered while the patient was using the insulin pump. If this information is not known, a weight based approximation can be made as a starting point of therapy.

Hospitalization is a dynamic state characterized by changes in clinical and nutritional status that affect insulin sensitivity. More frequent adjustments in insulin therapy than that required in the outpatient setting are usually indicated. At least daily review of bedside BG results is required for appropriate and timely adjustments in insulin therapy based on BG pattern and correction insulin use over last 24-48h:

If all premeal BG are 100 - 140mg/dl AND random BG <180mg/dl, make no change.

Basal insulin should be adjusted if fasting BG are consistently out of range.

Nutritional insulin should be adjusted or added to the preceding meal if premeal or bedtime BG are consistently out of range.

Peri-operative management of the diabetes patient

There are no studies defining the optimal range for BG during the peri-operative period. Maintaining BG levels between 80 - 110 mg/dl does not have any advantage over less stringent glycemic targets. BG targets of 140 - 180 mg/dl as previously described are reasonable for patients with diabetes or hyperglycemia undergoing surgical procedures.

There will be selected patients who are able to achieve or maintain BG levels between 70 - 140 mg/dl without intervention throughout a surgical procedure. In these situations, regular monitoring of BG allows for prompt intervention in the event of either hypoglycemia or hyperglycemia.

For patients with sustained elevations in BG > 140 mg/dl during the peri-operative period, monitored treatment with insulin is required to prevent more severe elevations in BG to > 180 mg/dl.

Rational modification of diabetes therapy prior to surgical procedures reduces the risk for hyperglycemia and hypoglycemia.

General anesthesia is more likely to be associated with exacerbations of hyperglycemia than spinal or local anesthesia.

There are three distinct phases of peri-operative glycemic management:

Pre-operative

Intra-operative

Post-operative

Pre-operative Glycemic Management

For patients treated with therapeutic lifestyle interventions, no specific preparation is needed. This group requires measurement of a BG on arrival in the SDS suite.

For patients treated with oral agents (see section on Pharmacologic (oral and injectable incretins) and Surgical Treatment of Diabetes.)

Take usual doses of medications up until the time nutritional status changes.

Hold oral agents the morning of surgery.

Check BG on arrival in SDS

Use SQ insulin to treat BG > 150 mg/dl

Oral agents can be resumed postoperatively when patient resumes usual oral intake and risk of liver, kidney, and heart failure is minimal.

For patients treated with non-insulin injectable therapies (glucagon-like peptide-1 agonists (incretins), pramlintide), these agents can usually be taken the day prior to surgery, as long as the patient is eating usual meals. Hold these agents on the day of surgery.

Table II.

Current hourly basal rate using insulin pump as compared to the starting rate for IV insulin

Current Hourly Basal Rate (using insulin pump)

Starting Rate for IV Inuslin (units/hour)

<0.5

0.5

0.5-1.5

1.0

1.5-2.5

2.0

>2.5

2.5

*The rationale for the differences in dose adjustments among the different basal insulin preparations is based on the different pharmacokinetic profiles of these preparations. Detemir acts like a long acting NPH insulin when dosed at concentrations ≥ 0.4 units/kg per day.

For patients treated with CSII, there are no studies investigating the safety and efficacy of allowing patients to use an insulin pump throughout a surgical procedure. Despite the absence of data, many institutions allow patients to continue to use this form of therapy during short term outpatient procedures. Careful monitoring of BG performed at hourly intervals allows for detection of hypoglycemia or hyperglycemia with appropriate interventions.

For short procedures, the patients may be allowed to continue insulin pump therapy. Treatment with IV glucose is indicated for BG < 100 mg/dl to prevent hypoglycemia. Additional treatment with SQ or IV insulin is indicated when BG exceeds 180 mg/dl. For long procedures with anticipated hospital admission, initiate IV insulin infusion in the pre-operative holding area at a rate based on usual pump basal rate.

The IV insulin infusion rate can be titrated at hourly intervals to achieve and maintain BG between 140 - 180 mg/dl. Discontinue insulin pump therapy within 30 minutes of initiation of IV insulin (precautions must be taken to prevent loss of the pump device by entrusting this with a family member or placing in a secure area).

Intra-operative glycemic management

Judicious use of correction or supplemental insulin administered via SQ or IV can be used to treat BG > 140 mg/dl as a way of maintaining glucose levels in the desired range of 140 - 180 mg/dl.

Table III illustrates one potential approach to the treatment of hyperglycemia with SQ insulin during surgical procedures. Frequent monitoring of BG is required.

Table III.

Suggested algorithm for peri-operative SQ insulin therapy

Blood Glucose (mg/dl)

Rapid Acting Insulin Dose

<70

Treatment for hypoglycemia

70-140

No treatment

141-180

2 units

181-220

4 units

221-260

6 units

262-300

8 units

301-340

10 units

> 340

12 units

IV insulin infusions are the most flexible method of achieving and maintaining glycemic control in the peri-operative period. The rapid onset of action and short half life of intravenously administered insulin allows rapid titration upward or downward in patients who experience hemodynamic instability during a surgical procedure. One suggested approach for IV insulin is included in Table IV.

Maintain a glucose source such, as 5 - 10% dextrose containing solutions, in patients receiving peri-operative insulin therapy. Monitor BG at least hourly using laboratory based methods. This is preferred over bedside glucose meters, which can produce erroneous results in patients who are anemic, polycythemic, or hypoxic. For patients undergoing prolonged surgical procedures, maintaining a consistent site for glucose measurements helps reduce variability in results.

Post-operative glycemic management

Check BG on arrival in the recovery room and/or SDS suite. For patients who will be discharged to home, resume usual treatment once the patient is awake and able to consume food.

For patients who required IV insulin during a surgical procedure, this can be discontinued following administration of SQ insulin according to Table IV. Once the patient is stable off the IV insulin infusion, discharge plans can be initiated.

For those patients who will be admitted to a critical care area from the operative suite, transition to an IV insulin infusion protocol specific to that unit targeting a BG 110 - 140 or 140 - 180 mg/dl. For patients who will be admitted to a general medical surgical critical care area from the operative suite, transition to scheduled insulin therapy. Many postoperative patients are not eating for the initial 24 hour time period. These patients can initially be treated with basal insulin in combination with correction insulin.

Planning for discharge from the hospital

Discharge planning begins at the time of hospital admission, with an assessment of the pre-admission glycemic control, which guides the need for adjustment of the outpatient diabetes regimen. In addition, hospitalization provides an opportunity to educate those patients who lack adequate dietary or diabetes education. Although not all education can be provided while patients are hospitalized, referral for diabetes education can be made at the time of hospital discharge. Education regarding diet, insulin administration, use of a glucometer, and recognition of hyperglycemic or hypoglycemic symptoms prior to discharge are reasonable topics.

Note that:

Patients with A1C >8% who have known diabetes will usually require adjustment of their pre-admission regimen.

Patients who are discharged on a new regimen of TPN, enteral nutrition, or high dose corticosteroids will require ongoing monitoring and adjustment of their diabetes regimen as these therapies change.

Timely follow up with a PCP or endocrinologist helps minimize risk for hypoglycemia or hyperglycemia that can result in need for readmission.

(This manuscript reviewed the data regarding inpatient management of diabetes and hyperglycemia through the year 2009 and provided a framework for glycemic goals, and methods for achieving these goals, in hospitalized patients with critical and non-critical illness.)

(This study is the largest intervention trial of patients with medical and surgical critical illness with and without diabetes. This study provides the basis for the AACE/ADA recommendations published in 2009, as the control group treated to maintain BG values between 140 - 180 mg/dl demonstrated a low risk for hypoglycemia and clinical outcomes (infection, mortality, LOS) that were no different from those who were treated to near normoglycemia at the expense of hypoglycemia.)

http://resources.aace.com.

(This website provides up to date resources for clinicians with listing of available IV insulin infusion protocols, protocols for use of scheduled SQ insulin, and transition protocols for IV to SQ insulin therapy.)

(This study investigated the safety and efficacy of using long acting insulin therapy in hospitalized patients receiving continuous or cycled EN, and demonstrated the superiority of using scheduled basal insulin over SSI alone.)

(This is the only published study investigating oral nutrition therapy in hospitalized patients as a contributor to glycemic control. BG results with a consistent carbohydrate diet are compared to those with a patient controlled diet.)

(This was the first of several studies by these investigators described the efficacy and safety of scheduled SQ BBI in medical inpatients with type 2 diabetes. These investigators have also published studies in surgical inpatients.)

(This is the only study investigating the efficacy of pre-operative recommendations for modification of diabetes therapy in patients undergoing elective surgical procedures. The safety of advising patients with diabetes to take a percentage of their usual insulin dose is reported.)

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